Hyperexpression of NOD2 in intestinal mast cells of Crohn's disease patients: preferential expression of inflammatory cell-recruiting molecules via NOD2 in mast cells.
NOD2, an intracellular sensor of bacteria-derived muramyl dipeptide (MDP) has been implicated as a key player in intestinal immune health and disease. Mast cells (MCs) have been reported to be increased in the gut of patients with inflammatory bowel disease. However, NOD2 expression and its role in human primary MCs are unknown. The number of NOD2(+) intestinal MCs was significantly increased in the Crohn's disease (CD) specimens compared to Ulcerative colitis (UC) specimens and controls. IFN-gamma upregulated NOD2 expression in MCs. CXCL10 and urokinase-type plasminogen activator (uPA) upregulation was specific to MCs activated by MDP compared to MCs activated by LPS and IgE/anti-IgE. MDP-induced upregulation of ICAM-1, VCAM-1, and uPA was specific to MCs compared to mononuclear cells. The number of CXCL10(+)NOD2(+) intestinal MCs was significantly increased in the CD patients. Our results suggest that NOD2(+) MCs have specific pathogenic roles that involve the recruitment of inflammatory cells in CD.
Okumura
Shigeru
S
Research Unit for Allergy Transcriptome, Research Center for Allergy and Immunology, RIKEN Yokohama Institute, Yokohama, Japan.
Yuki
Keisuke
K
Kobayashi
Ryota
R
Okamura
Shinichi
S
Ohmori
Kazumitsu
K
Saito
Hirohisa
H
Ra
Chisei
C
Okayama
Yoshimichi
Y
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000276:immunology / Q000378:metabolism; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D054357:Chemokine CXCL10 / Q000276:immunology / Q000378:metabolism; D003093:Colitis, Ulcerative / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D003424:Crohn Disease / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000276:immunology* / Q000473:pathology; D008297:Male; D008407:Mast Cells / Q000276:immunology* / Q000378:metabolism; D008875:Middle Aged; D053473:Nod2 Signaling Adaptor Protein / Q000276:immunology / Q000378:metabolism*; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology
D015415:Biomarkers; C114753:CXCL10 protein, human; D054357:Chemokine CXCL10; D053473:Nod2 Signaling Adaptor Protein; D000119:Acetylmuramyl-Alanyl-Isoglutamine